1. Field of the Invention
The present invention is broadly concerned with a method for producing a highly useful biologic through the viral immunization of an animal such as a goat. More particularly, it is concerned with such a production method, along with a method of treating mammals using the biologic, wherein, in preferred forms, the goat or other test animal is treated with a virus such as a parvovirus which is normally immunosuppressive in a permissive host.
2. DESCRIPTION OF THE PRIOR ART
Vaccines have been in use since Edward Jenner (1749-1823) first recognized that people exposed to non-virulent strains of microorganisms could be protected against infection by the related virulent strains. His vaccination of patients with exudate of cowpox sores provide those same patients with partial protection against smallpox. Numerous vaccines have subsequently been prepared and used in both humans and animals. Immunization has been accomplished by vaccination with a suspension of live, attenuated, or killed organisms or specific protein, glycoprotein or surface material from various bacteria, rickettsiae, or virusus. These would include vaccines against anthrax, rabies, typhoid, cholera, smallpox, measles, mumps, pertussis, plague, and polio. The vaccine in each case has been intended to provide protection against a specific pathogen. While vaccination may provide long term specific protection it may or may not produce short term immunosystem modulation. The immune system responds to challenge via vaccination or infection by increased activity. This may result in the short term production of antigen non-specific immunoregulatory modulators such as interferon, interleukins, and other various lymphokines.
The rationale for a system that becomes active only in response to a specific challenge is simple. If the immune system operated at a high pitch of activity all the time, it would age prematurely and no longer provide the systematic protection it was evolved to deliver. Another possible complication with an usually active immune system could be the initiation of auto-immune reactions in which the system starts acting against itself, resulting in the destruction of normal tissue. Arthritis is exemplary of this particular condition.
Increased activity of the immune system by virtue of improper regulation could furthermore result in an inability to elicit an appropriate response. As an example, a massive response to a splinter in a finger would be completely inappropriate, just as no response to a major infection would be equally inappropriate.
Immunomodulation may provide a regulatory-directed approach at self-healing, particularly with respect to such intractable diseases as cancer. For this to occur two minimal criteria must be met. The immune system must be sufficiently intact to respond to the regulator(s), and secondly, the system under appropriate stimulation must have T-cells, B-cells and Natural Killer cells present that are capable of responding to the target antigen(s) or cell(s). In such an instance, however, a nonspecific immunomodulator could potentially serve to "turn on" the immune system and initiate healing.
A number of immunomodulators have previously been isolated and described and these appear to belong to one of three general groups, namely the interferons, the interleukins and the corticosteroids and leukotrienes.
The interferons are a family of glycoproteins normally produced in response to a viral infection and are produced by leukocytes and fibroblasts. There are three main types, alpha, beta and gamma. They have molecular weights in the range of 15,000 to 40,000 daltons. Recently they have been produced by recombinant DNA techniques. The interferons have been found to have an absolute specie specificity, and are only effective in the specie that produced it.
The second group of immunomodulators are the interleukins. They are a family of glycoproteins that are produced by white cells. It is believed that the lymphokines cause the activation of Natural Killer cells and B-cells, and act in the initiation and propagation of the specific sequences of cellular interactions that are now recognized as the immune response. These growth promoters and activators participate in the generation of immunoreactive cells. The lymphokines are antigen non-specific in that they activate all T and B cells in anticipation of the presentation of an antigen or a cell. The apparent molecular weights are in the range of 15,000-50,000 daltons.
The third type of regulators are the corticosteroids and the leukotrienes, which act as regulators in inflammation. When produced in atypical amount, the leukotrienes can cause immediate type hypersensitivity and anaphylaxis. They are principally oxygenated products of archidonic acid. In contrast the corticosteroids decrease immune system activity. Both corticosteroids and leukotrienes are small molecular weight compounds in comparison to the interleukins and interferons.
All of the immulogical regulators produced commerically are extracts or concentrates of tissue culture fluids from mitogen stimulated lymphoid and myleloid cells. The exception to this had been the IL-2 which has been produced by genetic engineering. The other immulogical modulators that have been artificially produced are the interferons. The difficultly with each of these production methods is that the individual reagents being produced do not reproduce the plethoric effect seen in vivo. No practical method has heretofore been discovered to produce a plurality of the immunoregulators together in the same proportions as they would normally be produced in response to infection or cancer in situ. Additionally the cost of prior known production methods has been considerable, thereby further limiting the utility of immunomodulators.
Cardiovascular disease is one of the principal causes of death in the United States, accounting for approximately one million deaths a year. One of the main contributory factors to the development of coronary heart disease is the presence of high levels of serum cholesterol. While serum cholesterol concentrations may be altered by diet, in humans the majority of cholesterol is synthesized in the liver and then distributed by low density lipoproteins. As a consequence, control of serum cholesterol concentrations solely by diet alone is very difficult if not impossible.
Currently there is only one medication, Cholestyramine, that has proven to be effective in lowering high serum cholesterol concentrations. Cholestyramine is an anion exchange resin that binds bile acids, resulting in a decreased reabsorption of the bile acids and the associated dietary cholesterol that they would normally carry back via the liver portal system. While use of Cholestyramine is indicated in certain patients, its use is limited because it may cause further increases in the serum triglyceride levels.